FEVER

DEFINITION OF FEVER
 Fever is an elevation of body temperature
that exceeds the normal daily variation,
in conjunction with an increase in
hypothalamic set point
 VARIATION IN TEMPERATURE
 Anatomic variation
 Physiologic variation:
 Age
 Sex
 Exercise
 Circadianrhythm
 Underlying disorders
 NORMAL BODY TEMPERATURE
 Maximum normal oral temperature
At 6 AM : 37.2
At 4 PM : 37.7
 PHYSIOLOGY OF FEVER
 Pyrogens:
 Exogenous pyrogens:
Bacteria, Virus, Fungus, Allergen,…
 Endogenous pyrogen
Immune complex, lymphokine,…
 Major EPs: IL1, TNF, IL6
 PHYSIOLOGY OF FEVER
 Exogenous pyrogen Activated leukocytes
Endogenous pyrogen(IL1,TNF,…)
 Acute Phase Response
 Preoptic area of anterior hypothalamus (PGE2)
increase of set point =>
 Braincortex
 Vasoconstriction heat conservation
 Muscle contraction heat production FEVER
 ACUTE PHASE RESPONSE
 Metabolic changes
 Negative nitrogene balance
 Loss of body weight
 Altered synthesis of
hormones
 Hematologic alterations
 Leukocytosis
 Thrombocytosis
 Decreased erythrocytosis
 Altered hepatocyte function
(Acute phase reactants)
 C reactive protein(increased)
 Serum amyloid A(increased)
 Fibrinogen(increased)
 Fibronectin(increased)
 Haptoglobin(increased)
 Ceruloplasmin(increased)
 Ferritin(increased)
 Albumin(decreased)
 Transferrin(decreased)
 HYPERTHERMIA
Heat production exceeds heat loss, and
the temperature exceeds the individuals
set point
 CAUSES OF HYPERTHERMIA
SYNDROME
 Heat stroke: Exercise, Anticholinergic
 Drug induced: Cocaine, Amphetamine,MAO inh.
 Neuroleptic malignant syndrome:Phenothiazine
 Malignant hyperthermia: Inhalational anesthetics
 Endocrinopathy: throtoxicosis, pheochromocytoma
 DIAGNOSIS OF HYPERTHERMIA

History
Antipyretics are not effective
Skin is hot but dry
 TREATMENT OF FEVER

Most fevers are associated with

self-limited infections, most

commonly of viral origin.

 TREATMENT OF FEVER
 Reasons not to treat fever:
 The growth and virulance of some organisms
 Host defense-related response
 Fever is an indicator of disease
 Adverse effect of antipyretic drugs
 Iatrogenic stress
 Social benefits
 DISCOMFORT DUE TO FEVER
 For each 1 °C elevation of body temperature:
Metabolic rate increase 10-15%
Insensible water loss increase
300-500ml/m2/day
O2 consumption increase 13%
Heart rate increase 10-15/min
 TREATMENT OF FEVER
 Reasons to treat fever:
 The elderly individual with pulmonary or cardiovascular disease
 The patient at additional risk from the hypercatabolic state (Poor
nutrition, Dehydration)
 The young child with a history of febrile convulsions
 Toxic encephalopathy or delirium
 Pregnant women (contraversy)
 For the patient comfort
 Hyperpyrexia
 Treatment Strategies
 Acetaminophen is generally a first-line
antipyretic due to being well tolerated
with minimal side effects.
 Pediatric dose: 10-15mg/kg q4-6h (2400mg/day);
adult: 650mg q 4 h(4000mg)
 Can be hepatotoxic in high doses; can upset stomach
 Clinical Pearls
Don’t give aspirin to children under
18 years (Reye’s Syndrome)

Try water sponge bath; remove

blankets and heavy clothing; keep
room at comfortable temp
 ATTENUETED FEVER RESPONSE
 Fever may not be present despite infection in:
Newborn
Elderly
Uremia
Significantmalnourished individual
Taking corticosteroids
 DRUG FEVER
 PATHOGENEGIS
 Contamination of the drug with a pyrogen or
microorganism
 Pharmacologic action of the drug itself
 Allergic (hypersensitivity) reaction to the drug
 DRUG FEVER
 Feverout of proportion to clinical picture
 Associated findings:
 Rigor(43%), Myalgia (25%), Rash (18%),
Headache (18%),
 Leukocytosis (22%), Eosinophilia (22%),
Serum sickness,Proteinuria Abnormal liver
function test
 DRUG FEVER
 Onset and duration:
 Onset: 1-3 weeks after the start of therapy
 Duration: remits 2-3 days after therapy is stoped
APPROACH TO THE PATIENT WITH
FEVER

ACUTE FEBRILE ILLNESS

 APPROACH TO FEVER
 Personal History:
 Age
 Occupation
 Placeof origin,Travel History
 Habits
 Sexual Practices
 Injection Drug Abuse
 Excessive Alcohol Use
 Consumption of Unpasteurized Dairy Products
 APPROACH TO FEVER
 Underlying Diseases:
 Splenectomy
 SurgicalImplantation of Prosthesis
 Immunodeficiency
 Chronic Diseases:
 Cirrhosis
 Chronic Heart Diseases
 Chronic Lung Diseases
 APPROACH TO FEVER
 Drug History:
 Antipyretics
 Immunosuppressants
 Antibiotics

 Family History:
 TB in the Family
 Recent Infection in the Family
 APPROACH TO FEVER
 Associated Symptoms:
 Shaking chills
 Ear pain,Ear drainage,Hearing loss
 Visual and Eye Symptoms
 Sore Throat
 Chest and Pulmonary Symptoms
 Abdominal Symptoms
 Back pain, Joint or Skeletal pain
 PATTERN OF FEVER
 Sustained (Continuous) Fever
 Intermittent Fever (Hectic Fever)
 Remittent Fever
 Relapsing Fever:
 Tertian Fever
 Quartan Fever
 Days of Fever Followed by a Several Days Afebrile
 Pel Ebstein Fever
 Fever Every 21 Day
 APPROACH TO FEVER

 Physical Examination:
 Vital Signs
 Neurological Exam.
 Skin Lesions,Mucous Membrane
 Eyes
 ENT
 Lymphadenopathy
 Lungs and Heart
 Abdominal Region (Hepatomegaly,Splenomegaly)
 Musculoskeletal
 LABORATORY STUDY
IN PATIENT WITH FEBRILE ILLNESS
Assess the extent and severity of the
inflammatory response to infection
Determine the site(s) and complications
of organ involvement by the process
Determine the etiology of the infectious
disease
 Initial Laboratory Evaluations in
UNEXPLAINED PROLONGED FEVER
 CBC (diff.)
 PBS for Malaria and borelia
 Two Blood Culture in 30 min. Interval
 CXR
 U/A
 L.F.T. in selected patients
 Wright in selected patients
 INDICATIONS OF HOSPITALISATION
IN PATIENT WITH FEBRILE ILLNESS
 Persons who are clinically unstable or are at risk
for rapid deterioration
 Major alterations of immunity
 Need for IV Antimicrobials or other fluids
 Advanced age
 FUO
FEVER OF UNKNOWN
ORIGIN
 FUO
ClassicFUO
Nosocomial FUO
Neutropenic FUO
HIV-Associated FUO
 Classic FUO
 Definition:
Fever of 38.3 C or higher on several
occasions
Fever of more than 3 weeks duration
Diagnosis uncertain, despite appropriate
investigations after at least 3 outpatient
visits or at least 3 days in hospital
 Nosocomial FUO
 Definition:
Fever of 38.3 or higher on several
occasions
Infection was not manifest or incubating
on admission
Failure to reach a diagnosis despite 3 days
of appropriate investigation in hospitalized
patient
 Neutropenic FUO
 Definition:
Fever of 38.3 or higher on several
occasions
Neutrophil count is <500/mm3 or is
expected to fall to that level in 1 to 2 days
Failure to reach a diagnosis despite 3 days
of appropriate investigation
 HIV-Associated FUO
 Definition:
Fever of 38.3 or higher on several
occasions
Fever of more than 3 weeks for outpatients
or more than 3 days for hospitalized
patients with HIV infection
Failure to reach a diagnosis despite 3days
of appropriate investigation
 Causes of classical FUO
Infections 22-58%

Neoplasms up to 30%

Noninfectiouse up to 25%
inflammatory diseases
Miscellaneous causes up to 25%

Undiagnosed up to 30%
 Infections commonly associated with
FUO
 Localized pyogenic infections
 Intravascular infections
 Systemic bacterial infections (Tuberculosis,
Brucellosis,…)
 Fungal infections
 Viral infections
 Parasitic infections
 Malignancies commonly associated with
FUO
 Hodgkin’s disease
 Non-hodgkin’s lymphoma
 Leukemia
 Renal cell carcinoma
 Hepatoma
 Colon carcinoma
 Atrial myxoma
Noninfectious inflammatory diseases
with FUO
 Collagen vascular/  Granulomatouse diseases
hypersensitivity diseases  Crohn’s disease
 Lupus
 Sarcoidosis
 Still’s
disease  Idiopathic
 Temporal arteritis granulomatouse
(Giant cell arteritis) disease
Miscellaneous causes of FUO
Drug fever
Factitious fever
FMF
Recurrent pulmonary emboli
Subacute thyroiditis
 FACTITIOUS FEVER
 Diagnosis should be considered in any FUO,
especially in:
Young women
Persons with medical training
If the patients clinically well
Disparity between temperature and pulse
Absence of the normal diurnal pattern
 Causes of FUO lasting > 6 month
Undiagnosed 19%
Miscellaneous 13%
Factitious 9%
Granulomatouse hepatitis 8%
Neoplasm 7%
Infection 6%
No fever 27%
 Approach to FUO
Determine whether the patient has a
true FUO
Workup of true FUO:
 Careful history
 Serial follow-up histories

 Careful physical examination

 Physical examination should be repeated
 Laboratory examination:
 CBC(diff)  Culture of blood,
 PBS urine,…
 ESR  Skin test

 U/A  Serology

 S/E  ANA
 Imaging:
CXR
Ultrasonography
Radiographic contrast study
Radioneuclide scan
CT or MRI
 Invasive Procedures
Biopsies:
Bone marrow
Skin lesion
Lymph node
Liver
Temporal artery